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t(4;11)(q21;q23) KMT2A/AFF1

Identity

 
  t(4;11)(q21;q23) ) G-banding (left) - Courtesy Diane H. Norback, Eric B. Johnson, and Sara Morrison-Delap, http://www.slh.wisc.edu/cytogenetics>; R- banding (right) - Jean Loup Huret (top), - Courtesy Christiane Charrin (middle), - Courtesy Hossein Mossafa (bottom and FISH).

Clinics and Pathology

Disease ALL mainly
Phenotype / cell stem origin B-ALL (L1 or L2), biphenotypic AL, at times ANLL (M4/M5 types maily); has been found in treatment related leukaemia; T-ALL as an exception
Epidemiology children (including infants: named a congenital leukaemia when before 1 yr or 2 yrs of age) and adults; half cases are under 4 yrs, 1/3 under 1yr; unbalanced sex ratio in cases < 4 yrs (1M/2F); 2 to 5% of ALL
Clinics organomegaly, CNS involvement not rare; can be secondary to epipodophyllotoxins (antitopoisomerase drugs for various cancers treatment); high WBC (median around 200 X 109/l), anaemia, thrombocytopenia; 90% blasts in blood
Cytology typically CD19+; may be accompanied with myeloid markers
Treatment bone marrow transplantation is highly indicated, as the prognosis is very poor
Prognosis CR is obtained but is promptly followed by relape; median survival: 7 mths in adult cases, 9 mths in children

Cytogenetics

 
  i(7q) R- banding - Jean-Loup Huret (left), - Courtesy Christiane Charrin (right).
Additional anomalies in 1/4 of cases at diagnosis, clonal evolution to hyperploidy: i(7q) in 10%, +X, + Mar, +6, +8, +19, +21, +13, +10, +14; no difference in outcome
Variants three way complex t(4;11;Var) exist and showed that the crucial event lies on der(11)

Genes involved and Proteins

Gene Name AF4
Location 4q21
Dna / Rna 10.5-12 kb mRNA
Protein contains a nuclear targeting sequence; nuclear localisation; function: transcription activator
Gene Name MLL
Location 11q23
Dna / Rna 21 exons, spanning over 100 kb; 13-15 kb mRNA
Protein 431 kDa; contains two DNA binding motifs (a AT hook, and Zinc fingers), a DNA methyl transferase motif, a bromodomain; transcriptional regulatory factor; nuclear localisation

Result of the chromosomal anomaly

Hybrid gene
Description 5' MLL-3' AF4; variable breakpoints
Transcript 12kb
  
Fusion Protein
Description e.g. 2319 amino acids; 240 kDa; N-term AT hook and DNA methyltransferase from MLL fused to AF4 C-term; the reciprocal ( AF4-MLL) may or may not be expressed; quite similar to the MLL/ENL fusion protein found with t(11;19)
Expression Localisation nuclear localisation
  

To be noted

you may also have a glance at 11q23 rearrangements, which gives an overview of related diseases.

Other genes implicated (Data extracted from papers in the Atlas)

Genes AFF1 AFF4 BTK KMT2A

Translocations implicated (Data extracted from papers in the Atlas)

 t(4;11)(q21;q23) KMT2A/AFF1

External links

Mitelman database Mitelman database (CGAP - NCBI)
t(4;11)(q21;q23) - Mitelman database (CGAP - NCBI)

Bibliography

Cytogenetic features of infants less than 12 months of age at diagnosis of acute lymphoblastic leukemia: impact of the 11q23 breakpoint on outcome: a report of the Childrens Cancer Group.
Heerema NA, Arthur DC, Sather H, Albo V, Feusner J, Lange BJ, Steinherz PG, Zeltzer P, Hammond D, Reaman GH
Blood. 1994 ; 83 (8) : 2274-2284.
PMID 8161794
 
Clinical characteristics and treatment outcome of childhood acute lymphoblastic leukemia with the t(4;11)(q21;q23): a collaborative study of 40 cases.
Pui CH, Frankel LS, Carroll AJ, Raimondi SC, Shuster JJ, Head DR, Crist WM, Land VJ, Pullen DJ, Steuber CP
Blood. 1991 ; 77 (3) : 440-447.
PMID 1991161
 
Twenty-three cases of acute lymphoblastic leukemia with translocation t(4;11)(q21;q23): the implication of additional chromosomal aberrations.
Schoch C, Rieder H, Freund M, Hoelzer D, Riehm H, Fonatsch C
Annals of hematology. 1995 ; 70 (4) : 195-201.
PMID 7748964
 
Acute leukemia with chromosome translocation (4;11): 7 new patients and analysis of 71 cases.
Lampert F, Harbott J, Ludwig WD, Bartram CR, Ritter J, Gerein V, Neidhardt M, Mertens R, Graf N, Riehm H
Blut. 1987 ; 54 (6) : 325-335.
PMID 3496135
 
Acute leukemia with chromosome translocation (4;11): 7 new patients and analysis of 71 cases.
Lampert F, Harbott J, Ludwig WD, Bartram CR, Ritter J, Gerein V, Neidhardt M, Mertens R, Graf N, Riehm H
Blut. 1987 ; 54 (6) : 325-335.
PMID 3496135
 
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed

Contributor(s)

Written12-1997Jean-Loup Huret

Citation

This paper should be referenced as such :
Huret JL
t(4;11)(q21;q23) KMT2A/AFF1;
Atlas Genet Cytogenet Oncol Haematol. December 1997
Free online version   Free pdf version   [Bibliographic record ]
URL : http://AtlasGeneticsOncology.org/Anomalies/t0411.html

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indexed on : Sat Jul 26 14:18:10 CEST 2014


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